Incorporation fidelity of the viral RNA-dependent RNA polymerase: A kinetic, thermodynamic and structural perspective

Christian Castro, Jamie J. Arnold, Craig E. Cameron

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Positive-strand RNA viruses exist as a quasi-species due to the incorporation of mutations into the viral genome during replication by the virus-encoded RNA-dependent RNA polymerase (RdRP). Therefore, the RdRP is often described as a low-fidelity enzyme. However, until recently, a complete description of the kinetic, thermodynamic and structural basis for the nucleotide incorporation fidelity of the RdRP has not been available. In this article, we review the following: (i) the steps employed by the RdRP to incorporate a correct nucleotide; (ii) the steps that are employed by the RdRP for nucleotide selection; (iii) the structure-based hypothesis for nucleotide selection; (iv) the impact of sites remote from the active site on polymerase fidelity. Given the recent observation that RNA viruses exist on the threshold of error catastrophe, the studies reviewed herein suggest novel strategies to perturb RdRP fidelity that may lead ultimately to the development of antiviral agents to treat RNA virus infection.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalVirus Research
Volume107
Issue number2
DOIs
StatePublished - Feb 2005

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Virology
  • Infectious Diseases

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